Tissue levels and optimum dosage of vitamin C in guinea pigs.

Ascorbic acid mixed with the diet of guinea pigs achieved substantially higher maximum tissue concentrations of ascorbate than when ascorbic acid was administered orally once a day. A 0.5% w/w of ascorbic acid in the diet ensured a state close to maximal tissue steady-state levels of ascorbate. In guinea pigs fed a diet with a high content of saturated fatty acids or with 0.2% w/w of cholesterol, the highest rate of cholesterol transformation into bile acids and the lowest concentration of total lipids, cholesterol and triglycerides in blood serum and liver were found in the group fed a diet with 0.5% w/w of ascorbic acid as compared to the marginal-deficiency group and the group receiving 0.05% w/w of ascorbic acid in the diet. Maximal tissue steady-state levels of vitamin C are probably optimal for the guinea pigs' health.

Effect of oyster mushroom (Pleurotus ostreatus) on pathological changes in dimethylhydrazine-induced rat colon cancer.

The effect of 5% of dried oyster mushroom (Pleurotus ostreatus) in the diet on the dimethylhydrazine (DMH)-induced colon carcinogenesis was studied in male Wistar rats. DMH in a dose of 20 mg/kg of body weight was applied to animals once a week during a period of 12 weeks. Mushroom diet was applied either after treatment with DMH for another 21 weeks or during the whole experiment. Mushroom diet reduced significantly the incidence of lymphoid hyperplasia foci when mushroom was supplemented during the whole experiment. Tumour lesions could be characterized either as carcinoma in situ, or as infiltrating adenocarcinoma. Mushroom diet did not affect significantly the incidence of tumours. Nevertheless, a reduction in total number of tumours was observed in both groups of animals fed mushroom diet. A significant reduction of the number of tumour foci of the type carcinoma in situ was observed in animals fed the oyster mushroom during the whole experiment. Also these animals had the significantly lower number of aberrant crypt foci. Mushroom diet reduced the ornithine decarboxylase activity in the colon and in the liver when oyster mushroom diet was administered during the whole experiment.

Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats.

The effect of the dose of oyster mushroom in the diet (1.0, 2.5, and 5.0%) and of the period of application (8, 16, 28, and 52 wk) on cholesterol accumulation in blood and body organs was studied in weanling male Wistar rats fed a diet containing 0.3% cholesterol. Reduction of cholesterol in serum and body organs was found to be dependent on the amount of dietary oyster mushroom administered. A negative correlation between the mushroom dose and cholesterol level was found after 8 and 28 wk of feeding (r=-0.9821 and -0.9803, respectively; P < 0.02 for both cases). The dose of 1% oyster mushroom did not affect cholesterol levels in serum or body organs. A significant reduction of cholesterol levels was observed in serum (31-46%) and liver (25-30%) at a dose of 5% of oyster mushroom for all periods. Reduced cholesterol content in very low-density lipoproteins (VLDL) was also observed at this level. The highest dose of oyster mushroom induced a decrease in conjugated diene levels in erythrocytes and an increase in the levels of reduced glutathione in the liver and stimulated the activities of catalase and glutathione peroxidase in the liver in the final period of the experiment.

Effect of mushroom Pleurotus ostreatus and isolated fungal polysaccharide on serum and liver lipids in Syrian hamsters with hyperlipoproteinemia.

In Syrian hamsters, a diet with 44% of the calories being fat and containing 52 mg cholesterol (C)/100 g induced an accumulation of blood plasma and liver C and triacylglycerol (TG). In these animals, we studied the effect of dried whole mushroom (Pleurotus ostreatus, 2% in the diet, 6-mo experiment) and ethanol-insoluble residue and structurally defined fungal polysaccharide, both isolated from the mushroom (in both cases, 4% in the diet, 2-mo experiments) on C and TG concentration in serum and liver. Whole mushroom effectively retarded the increase in C and TG in both serum and liver throughout the experiment. The mushroom also reduced the content of all lipids in lipoproteins with densities of less than 1.006 to less than 1.063 g/ml. Very-low-density lipoproteins played a substantial role in the decrease (65-80%) in serum lipids. As a result, the lipoprotein concentration of the specified density classes was reduced by 45-60%, and the concentration of the serum lipoprotein pool was reduced by 40%. Neither the chemical composition of high-density lipoproteins nor their serum concentration was affected by the mushroom. Ethanol-insoluble mushroom residue did not significantly affect serum lipid levels, but it reduced liver TG content. Fungal polysaccharide lowered the C content in serum and liver.

Glutathione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans.

Glutathione S-transferase genotypes GSTT1, GSTM1, GSTP1 were characterised in 155 middle-aged men and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non-smokers. Smokers had on average significantly lower levels of Vitamin C, beta-carotene and beta-cryptoxanthin and higher amounts of oxidised purines and pyrimidines in lymphocyte DNA. The GSTM1 null genotype was associated with elevated glutathione as well as with higher Vitamin C concentration in plasma. Vitamin C was higher in GSTT1+ compared with GSTT1 null--as was glucose-6-phosphate dehydrogenase activity. The homozygous GSTP1 a/a genotype was associated with significantly higher levels of GST activity measured in lymphocytes, in comparison with the b/b genotype. Using multifactorial statistical analysis we found significant associations between smoking, GSTP1 genotype, plasma Vitamin C, and purine base damage in lymphocyte DNA. The difference in Vitamin C plasma levels between smokers and non-smokers was seen only with the GSTP1 b/b genotype. This group accounted also for most of the increase in purine oxidation in smokers. In contrast, the link between smoking and oxidised pyrimidines in DNA was seen only in the GSTT1 null group. It seems that polymorphisms in the phase II metabolising enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.

The mushroom Pleurotus ostreatus accelerates plasma very-low-density lipoprotein clearance in hypercholesterolemic rat.

The administration of a diet containing 5% of dried oyster mushroom to male Wistar rats fed a cholesterol diet (0.3%) shortly after weaning for 8 weeks reduced cholesterol levels in the serum and liver by 27 and 33%, respectively and increased the fractional turnover rate of 125I-very-low-density lipoproteins (VLDL) by more than 30%.

Dietary oyster mushroom (Pleurotus ostreatus) accelerates plasma cholesterol turnover in hypercholesterolaemic rat.

The effect of adding 5% powdered oyster mushroom (Pleurotus ostreatus) during 12 weeks on kinetic parameters of cholesterol metabolism was studied in male rats (Wistar, initial body weight 85 g) fed a semisynthetic diet containing 0.3% of cholesterol. The plasma cholesterol decay curve (examined for the final 29 days of the experiment after a single dose of cholesterol-4-14C) was evaluated by mathematical analysis using a two-pool model of plasma cholesterol metabolism. The oyster mushroom in the diet reduced the half-times of both exponentials resulting in lower calculated values (by 28%) of total entry of cholesterol into the body cholesterol pool (absorption+endogenous synthesis) and lower sizes of both pools (with slower and faster cholesterol exchange). The rate of cholesterol exchange between the pools was enhanced and the rate of total clearance of cholesterol from the system (metabolic turnover rate of cholesterol i.e. the rate of degradation and excretion of cholesterol from the organism) was enhanced by 50%. The oyster mushroom diet effectively prevented the progress of hypercholesterolaemia (decrease by 38%) and cholesterol accumulation in liver (decrease by 25%) that were induced by the cholesterol diet.

Dose-dependent hypocholesterolaemic effect of oyster mushroom (Pleurotus ostreatus) in rats.

A highly significant negative correlation (r=-0.981, p < 0.001) between the amount of oyster mushroom (Pleurotus ostreatus) in the diet and cholesterol levels in the serum has been found in male Wistar rats fed shortly after weaning by a a diet with 0.3% cholesterol. The addition of 1.0, 2.5 and 5.0% of oyster mushroom to the diet reduced the levels of serum cholesterol by 11, 31 and 46%, respectively. The diet containing 5% of oyster mushroom suppressed cholesterol accumulation in the liver and increased the fraction of cholesterol carried by high-density lipoproteins.

Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with insulin-dependent diabetes.

We have investigated the effect of a diet containing of 4% oyster fungus (Pleurotus ostreatus) and 0.1% cholesterol on glycaemia and hyperlipoproteinaemia in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two months, the rats with diabetes kept on the oyster fungus diet, had a significantly lower basal and postprandial glycaemia, the insulinaemia remained unchanged. The cholesterol concentration was decreased by more than 40%, the lipoprotein profile was upgraded by the decrease of the cholesterol in both the low density and very low density lipoproteins. The oyster fungus decreased the cholesterol accumulation in the liver and had no significant effects on the levels of serum and liver triacylglycerols.

Protein synthesis in growing and adult rats on casein and gluten nutrition.

Male weaning rats were put on a diet with a physiological nutrient combination adjusted for age, milk casein (E/N = 0.79) and wheat gluten (E/N = 0.30) being the sources of protein. The net protein ratio (NPR) was evaluated weekly until 140 days of age. On days 70 and 140, L-(U-14C)-tyrosine was administered intraperitoneally and 12 h later specific tyrosine activity was determined in the protein fraction of liver and muscle by measuring the incorporation of the labeled amino acid in order to assess protein synthesis over the corresponding time period. Regression lines describing the relationship between animals' weight, age and protein source suggested that the daily weight increase was 6.99 g between days 30-77, 2.97 g between days 77-105 and 0.64 g between days 105-140. Muscle tyrosine levels in rapidly growing animals aged 70 days were 91.0 micrograms/g/12 h for casein and 65.6 micrograms/g/12 h for gluten. Liver tyrosine levels were 336.4 and 189.6 micrograms/g/12 h, respectively. The differences observed at this age were highly significant. In adult animals (140 days old) there were non-significant differences between tyrosine levels in the casein- and gluten-fed groups. The isotope study clearly showed that protein synthesis was reduced in growing and developing animals on vegetable nutrition, which is deficient in essential amino acids, (especially the limiting amino acid lysine, crucial for the utilization of all other amino acids in peptide chain synthesis). The low rate of amino acid utilization found in animals younger than 105 days is consistent with the findings obtained by the isotope method.

Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with insulin-dependent diabetes.

We have investigated the effect of a diet containing of 4% oyster fungus (Pleurotus ostreatus) and 0.1% cholesterol on glycaemia and hyperlipoproteinaemia in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two months, the rats with diabetes kept on the oyster fungus diet, had a significantly lower basal and postprandial glycaemia, the insulinaemia remained unchanged. The cholesterol concentration was decreased by more than 40%, the lipoprotein profile was upgraded by the decrease of the cholesterol in both the low density and very low density lipoproteins. The oyster fungus decreased the cholesterol accumulation in the liver and had no significant effects on the levels of serum and liver triacylglycerols.

Antioxidative state of the myocardium and kidneys in acute diabetic rats.

The influence of acute diabetes (8 days), induced by streptozotocin (45 mg.kg-1 body weight) on myocardial and renal antioxidative conditions was investigated. The animals were given subtherapeutical doses of insulin (Interdep 6 U. kg-1 body weight, s.c.). Considerably increased levels of malondialdehyde (MDA), as well as of superoxide dismutase (SOD) and catalase (CAT) activity were found in the myocardium of diabetic animals. The oxidized glutathione (GSSG) level and glutathione peroxidase (GSH-PX) activity remained unchanged. The reduced glutathione (GSH) level as well as the activity of glutathione S-transferase (GST) were significantly lower. The activity of GSH-PX in the kidneys of diabetic rats increased by 60% and that of GST by 105%, respectively. CAT and SOD activity values were unchanged.

Effect of oyster fungus (Pleurotus ostreatus) on serum and liver lipids of Syrian hamsters with a chronic alcohol intake.

The authors studied the effect of oyster fungus (Pleurotus ostreatus) (2% dried fruiting bodies in a standard diet) on the serum and liver lipids of growing male Syrian hamsters with a chronic alcohol intake (a 15% aqueous solution). After eight weeks' alcohol intake there was an increase in their serum cholesterol, triacylglycerol (TG) and phospholipid (PL) concentration, 40 - 60% of which was accounted for by an increase in the very low density lipoprotein (VLDL) concentration. The proportion of VLDL in the lipoprotein pool rose by almost 15%, whereas the proportion of high density lipoproteins (HDL) fell. The simultaneous administration of the fungus in the diet reduced the cholesterol level below the value in the control animals not given any alcohol. Both the serum TG and the VLDL concentration fell by 30%, but neither the chemical composition and concentration of the HDL nor the cholesterol concentration were affected. The addition of the fungus to the diet completely abolished the increase induced in the liver cholesterol and TG concentration by the chronic intake of alcohol.

The effect of dietary protein and sucrose on the diabetic rat kidney.

The effect of 3 months feeding with diets of different protein and sucrose content (9% casein + 70% sucrose vs. 18% casein + 61% sucrose) on the development of diabetic nephropathy and changes in serum lipid spectrum was investigated in rats with insulin-dependent diabetes (streptozotocin 45 mg.kg-1). Metabolism of diabetic animals (before the nutritional regimen) was characterized by hyperglycaemia, moderate hyperlipidemia, lipid accumulation in the liver and elevated creatinine concentration in the blood. Kidney weight and protein content were not significantly changed. Histological picture of kidneys showed initial changes of glomerular structure. After three months hyperlipoproteinaemia was more accentuated in animals given either of the two diets, the kidneys were hypertrophic with a higher protein content and displayed morphological changes of diabetic nephropathy. Animals given the low-protein diet developed smaller morphological changes both in glomeruli and tubuli. The study indicates that dietary protein and not hyperlipoproteinaemia is the major factor, which may significantly influence the progress of diabetic nephropathy.

Effects of pleuran (beta-glucan isolated from Pleurotus ostreatus) on experimental colitis in rats.

The effects of pleuran, beta-1,3 glucan isolated from Pleurotus ostreatus, were studied in a model of acute colitis induced by intracolonic administration of acetic acid. There was a reduction of the colonic damage score, colonic wet weight and wet/dry weight ratio 48 h after single luminal 2% pleuran suspension pretreatment. Similar results were obtained after repeated intraperitoneal administration of pleuran in doses of 30 and 100 mg/kg. Pleuran given orally as a 10% food component over 4 weeks was effective in reducing the extent of mucosal damage, but did not prevent the increase of myeloperoxidase in the injured colonic segment. In the segment without macroscopic evidence of inflammation, myeloperoxidase activity was significantly lower as documented by histological examination. The results indicate a possible role of this immunomodulator in the treatment of ulcerative colitis.

Dietary tomato and grape pomace in rats: effect on lipids in serum and liver, and on antioxidant status.

Addition of tomato and grape pomace to the cholesterol (0.3%) diet of male Wistar rats produced a dose-dependent effect. During the eight-week experiment, 5% pomace showed no effect; however, 15% pomace reduced serum cholesterol levels from 4.4 mmol/L to 2.5 mmol/L (tomato) and 2.0 mmol/L (grape). At a concentration of 15%, both tomato and grape pomace induced a redistribution of cholesterol in lipoproteins, resulting in a pronounced anti-atherogenic profile: reduced cholesterol concentration in very-low-density lipoprotein (VDL) (24% [tomato], 50% [grape]) and low-density lipoprotein (LDL) (3-fold, 3.6-fold). In addition, grape pomace increased cholesterol concentration in high-density lipoprotein (HDL) by 26%. Both types of pomace reduced the VLDL and LDL contribution to cholesterol transport in favour of HDL. Grape pomace (15%) produced a significant reduction in cholesterol and triacylglycerols in the liver and serum respectively. Diets containing tomato and grape pomace reduced plasma levels of conjugated dienes by 30-50%, and showed a tendency towards higher superoxide dismutase and glutathione peroxidase activity in the liver.

Effect of pleuran (beta-glucan from Pleurotus ostreatus) on the antioxidant status of the organism and on dimethylhydrazine-induced precancerous lesions in rat colon.

The effect of pleuran (beta-1,3-D-glucan isolated from the oyster mushroom Pleurotus ostreatus) on the antioxidant status of the organism and on the development of precancerous aberrant crypt foci (ACF) lesions in the colon is studied in the male Wistar rat. A diet containing either 10% pleuran or 10% cellulose was compared with a cellulose-free diet and both were found to significantly reduced conjugated diene content in erythrocytes and in liver. Particularly significant was the reduction of conjugated dienes in the colon following pleuran administration. Diets containing cellulose and pleuran reduced glutathione peroxidase (GSH-PX) activity and increased catalase activity in erythrocytes. Pleuran increased superoxide dismutase (SOD) and GSH-PX activity (compared with the cellulose diet), and glutathione reductase activity (compared with the cellulose-free diet) in liver; and both diets reduced glutathione levels significantly in the colon. ACF lesions developed in the colon of all animals fed a cellulose-free diet; however, the incidence was reduced to 64% and 60% following the cellulose and pleuran diets, respectively. The highest average count of the most frequent small ACF lesions--and highest total count--was seen in animals fed a cellulose-free diet. Although ACF lesions were reduced by the cellulose diet, the more significant reduction statistically (>50%) was achieved with the pleuran diet.

Natural hypocholesterolemic agent: pectin plus ascorbic acid.

An addition of 5% citrus pectin and 0.5% ascorbic acid to high-fat diet of guinea pigs prevented total cholesterol accumulation in blood serum and the liver. Two groups of persons were given a preparation containing a daily dose of 15 g pectin and 450 mg ascorbic acid for 6 weeks. In 21 healthy persons with mild hypercholesterolemia total serum cholesterol dropped significantly by 24 mg/100 ml (8.6%), while the concentration of high density lipoprotein cholesterol remained unchanged. In 11 hyperlipemic outpatients (type IIa, IIb and IV) total serum cholesterol dropped by 68 mg/100 ml (18.7%). The changes in triglyceridemia proved inconsistent.

[Progressive infantile spinal muscular atrophy. Report of 12 cases]. / Atrofia muscular espinhal infantil progressiva. Relato de 12 casos.

Twelve children with progressive spinal muscular atrophy were seen at Santo Antonio Children Hospital, Porto Alegre. Diagnosis was based on neurological evaluation, serum enzymes, electroneuromyography and muscle biopsy. Several aspects are discussed by the authors, especially those concerning the presentation mode of the illness and the laboratory investigation. Our results are reviewed under the light of the current literature.

Evaluation of bronchoalveolar lavage fluid cytotoxic parameters after inhalation exposure to amosite and wollastonite fibrous dusts combined with cigarette smoke.

The aim of this work was to compare the influence of amosite-asbestos and wollastonite fibrous dusts combined with cigarette smoke on chosen cytotoxic parameters of bronchoalveolar lavage fluid (BALF) in rats. Fisher 344 rats inhaled wollastonite or amosite fibrous dusts (60 or 30 mg x m(-3) air) one hour every two days combined with daily breathing of diluted mainstream tobacco smoke (30 mg of TPM x m(-3) air). The experiment lasted 6 months. After sacrifying the animals bronchoalveolar lavage (BAL) was performed and the viability and phagocytic activity of alveolar macrophages (AM), lactate dehydrogenase (LDH) and alkaline phosphatase activity (in the cell-free BALF), acid phosphatase (ACP) and cathepsin D activity (in cell-free BALF and BAL cell suspension) were examined. Exposure to amosite without tobacco smoke significantly decreased the viability of AM and increased the cathepsin D activity in BAL cells. Exposure to wollastonite significantly increased only the cathepsin D activity in BAL cells. Smoking significantly depressed the phagocytic activity of AM and amplified the amosite-induced increase of lysosomal enzyme activities--especially the activity of cathepsin D in BAL cells.